實(shí)驗(yàn)十七苯片吶醇的制備及

實(shí)驗(yàn)十七苯片吶醇的制備一、實(shí)驗(yàn)?zāi)康?、學(xué)習(xí)苯環(huán)支鏈上的氧化反應(yīng)2、掌握減壓過(guò)濾和重結(jié)晶提純的方法

二、實(shí)驗(yàn)原理三、實(shí)驗(yàn)儀器和藥品天平、量筒、圓底燒瓶、冷凝管、電爐、布氏漏斗、抽濾瓶、甲苯、高錳酸鉀、濃鹽酸、沸石、活性炭

四、實(shí)驗(yàn)步驟1、在燒瓶中放入2.7ml甲苯和100ml蒸餾水，瓶口裝上冷凝管，加熱知沸騰。經(jīng)冷凝管上口分批加入8.5g高錳酸鉀。黏附在冷凝管內(nèi)壁的高錳酸鉀用25ml水沖入燒瓶中，繼續(xù)煮沸至甲苯層消失，回流液中不再出現(xiàn)油珠為止。2、反應(yīng)混合物趁熱過(guò)濾，用少量熱水洗滌濾渣，合并濾液和洗滌液，并放入冷水浴中冷卻，然后用濃鹽酸酸化至苯甲酸全部析出為止（若濾液呈紫色加入亞硫酸氫鈉除去）。3、將所得濾液用布氏漏斗過(guò)濾，所得晶體置于沸水中充分溶解（若有顏色加入活性炭除去），然后趁熱過(guò)濾除去不溶雜質(zhì)，濾液置于冰水浴中重結(jié)晶抽濾，壓干后稱重?；亓餮b置圖

五、實(shí)驗(yàn)數(shù)據(jù)處理

六、思考題反應(yīng)完畢后，若濾液呈紫色。加入亞硫酸氫鈉有何作用？亞硫酸氫鈉可以和高錳酸鉀反應(yīng)，消耗多余的高錳酸鉀，生成二氧化錳，溶液紫色褪去，產(chǎn)生棕色沉淀。簡(jiǎn)述重結(jié)晶的操作過(guò)程選擇溶劑→溶解固體→除去雜質(zhì)→晶體析出→晶體的收集與洗滌→晶體的干燥①將待重結(jié)晶的物質(zhì)溶解在合適的溶劑中，制成過(guò)飽和溶液。②若待重結(jié)晶物質(zhì)含有色雜質(zhì)，可加活性碳煮沸脫色。③趁熱過(guò)濾以除去不溶物質(zhì)及活性碳。④冷卻濾液，使晶體從過(guò)飽和溶液中析出，而可溶性雜質(zhì)仍保留在溶液里。⑤減壓過(guò)濾，把晶體從母液中分離出來(lái)，洗滌晶體以除去吸附在晶體表面上的母液。在制備苯甲酸過(guò)程中，加料高錳酸鉀時(shí)，如何避免瓶口附著？實(shí)驗(yàn)完畢后，粘附在瓶壁上的黑色固體物是什么？如何除去？答：可借助粗頸漏斗或?qū)⒎Q量紙疊成喇叭狀將研細(xì)的固體物體加入瓶中。粘附在壁上的黑色固體物為二氧化錳，簡(jiǎn)單的除去方法為：加入稀的亞硫酸鈉溶液，輕輕震蕩可除去二氧化錳，其原理為氧化還原機(jī)理。

七、注意：一定要等反應(yīng)液沸騰后（高錳酸鉀只溶于水不溶于有機(jī)溶劑），高錳酸鉀分批加入，避免反應(yīng)激烈從回流管上端噴出。在苯甲酸的制備中，抽濾得到的濾液呈紫色是由于里面還有高錳酸鉀，可加入亞硫酸氫鈉將其除去。真題再現(xiàn)現(xiàn)有甲苯用高錳酸鉀氧化制得的粗苯甲酸5g，其中含有少量雜質(zhì)，并帶有顏色。通常情況下苯甲酸為白色晶體,密度1.27，mp122℃，微溶于冷水，溶于沸水，乙醇，乙醚，氯仿，苯等溶劑。請(qǐng)用重結(jié)晶方法提純苯甲酸，敘述操作過(guò)程。（北京理工大學(xué)2006年）（1）取5g粗苯甲酸,放入150mL錐形瓶中，加入一定量的水，石棉網(wǎng)上加熱至沸騰,等固體完全溶解。若有尚未完全溶解的固體，可繼續(xù)加入少量熱水，每次少量，直至完全溶解后,再多加2~3mL水，移去火源，稍冷后加入少許活性炭,稍加攪拌后繼續(xù)加熱5～10min。（2）安裝好預(yù)熱過(guò)的抽濾轉(zhuǎn)裝置,將上述熱溶液趁熱抽濾,濾液倒入干凈的燒杯中,慢慢冷卻至室溫,待晶體完全析出后,再進(jìn)行抽濾,用少量水洗滌漏斗中的晶體,用玻璃塞擠壓晶體,直至抽干。取出晶體,放在培養(yǎng)皿中攤開(kāi)晾干或用紅外燈烘干,稱重計(jì)算收率。

實(shí)驗(yàn)十五、十六二苯甲醇的制備二苯甲醇，常溫下白色至淺米色結(jié)晶固體，熔點(diǎn)69℃。易溶于乙醇、醚、氯仿和二硫化碳，幾乎不溶于冷的粗汽油，20℃水中溶解度僅為0.5g/L。低毒，缺乏有關(guān)毒性數(shù)據(jù)，可參照甲醇毒性，避免與皮膚和眼睛接觸。明火、高溫、遇強(qiáng)氧化劑可著火燃燒，釋放出有毒氣體。

二苯甲醇主要用于有機(jī)合成，醫(yī)藥工業(yè)中間體?？勺鳛榭惯^(guò)敏藥物苯海拉明、帕金森藥物苯甲托品的中間體。二苯甲醇用還原二苯甲酮的方法制備，還原方法有很多種，實(shí)驗(yàn)室常用的有硼氫化鈉還原及堿性條件下以鋅粉還原。方法一硼氫化鈉還原法該法屬于金屬氫化物還原，由金屬氫化物提供負(fù)氫離子還原羰基。類似的金屬氫化物還有氫化鋁鋰、三叔丁氧基氫化鋁鋰；硼氫化鈉，性質(zhì)溫和，可在水或醇溶液中反應(yīng)；選擇性高，不還原雙鍵、三鍵，一般也不還原酯，酰胺，羧酸及腈。方法二鋅粉還原法該法是活潑金屬單分子還原法，底物接受金屬一個(gè)電子生成負(fù)離子自由基，再接受一個(gè)電子生成二價(jià)負(fù)離子，最后與質(zhì)子結(jié)合生成醇。金屬還可選擇鈉、鋰、鎂、鐵、錫等。鋅的還原性和價(jià)格都適中，反應(yīng)條件溫和，后處理簡(jiǎn)單。兩種方法的具體操作稍有不同，詳細(xì)過(guò)程如下：方法一在裝有回流冷凝管的25毫升圓底燒瓶中，加入1.83克二苯甲酮和8毫升甲醇，搖動(dòng)使其溶解，迅速稱取0.23克硼氫化鈉加入瓶中，搖動(dòng)使之溶解；反應(yīng)物自然升溫至沸騰，室溫下放置20分鐘，不時(shí)振蕩，入3毫升水，加熱至沸，保持5分鐘；冷卻，析出結(jié)晶。抽濾，粗品干燥后以石油醚重結(jié)晶，干燥后得白色針狀晶體，稱重，計(jì)算收率，測(cè)熔點(diǎn)。方法二在裝有冷凝管和攪拌磁子的50毫升燒瓶中，依次加入2.0克氫氧化鈉、1.83克二苯甲酮、2克鋅粉、20毫升95%乙醇，充分振蕩，使氫氧化鈉和二苯甲酮逐漸溶解。反應(yīng)微放熱，約20分鐘后，以80℃溫度加熱攪拌2小時(shí)；反應(yīng)物冷卻后，抽濾，固體以少量乙醇洗滌，濾液倒入80毫升事先用冰水冷卻的水中，搖蕩混勻后以濃鹽酸小心酸化，使pH=5~6，抽濾；粗產(chǎn)物干燥后，以15毫升石油醚重結(jié)晶，得針狀晶體，干燥，稱重，計(jì)算收率，測(cè)熔點(diǎn)。實(shí)驗(yàn)過(guò)程中，請(qǐng)大家注意以下事項(xiàng)：硼氫化鈉有一定腐蝕性，稱量時(shí)小心操作，不要接觸皮膚，也不要吸入顆粒或粉末；二苯甲醇粗品應(yīng)干燥徹底后再進(jìn)行重結(jié)晶，否則水分會(huì)影響重結(jié)晶過(guò)程；酸化時(shí)溶液酸性不宜太強(qiáng)，否則晶體難以析出。

等離子體電化學(xué)通過(guò)片納醇偶聯(lián)形成碳-碳鍵醛酮片醇偶聯(lián)形成碳-碳鍵需要較大的負(fù)還原電位，通常用化學(xué)計(jì)量還原試劑來(lái)實(shí)現(xiàn)。在這里，我們使用通過(guò)等離子液相過(guò)程產(chǎn)生的溶劑化電子。對(duì)甲基-4-甲酰基苯甲酸酯的參數(shù)研究表明，在競(jìng)爭(zhēng)還原成酒精的選擇性需要對(duì)質(zhì)量運(yùn)輸?shù)男⌒目刂?。這種通用性在苯甲醛、苯酮和糠醛中得到了證明。反應(yīng)擴(kuò)散模型解釋了觀察到的動(dòng)力學(xué)，從頭計(jì)算提供了對(duì)機(jī)理的洞察力。這項(xiàng)研究為還原有機(jī)反應(yīng)提供了一種無(wú)金屬、電力、可持續(xù)的方法。圖1。實(shí)驗(yàn)產(chǎn)率(紅方框)和模型結(jié)果(虛線)在MFB等離子-液體過(guò)程中得到的片納醇產(chǎn)品作為(a)反應(yīng)時(shí)間和(B)電流的函數(shù)。MFB初始濃度為0.12M，電流為2.3mA，反應(yīng)時(shí)間為4h，甲醇(MeOH)與水的體積比為5:1。用核磁共振氫譜測(cè)定產(chǎn)率。誤差條代表了六個(gè)獨(dú)立試驗(yàn)的標(biāo)準(zhǔn)差。圖2。(A)MFB的摩爾轉(zhuǎn)化率隨初始MFB濃度的變化;(B)產(chǎn)物產(chǎn)率與甲醇/水體積比的關(guān)系;(C)片那醇產(chǎn)品的法拉第效率隨初始MFB濃度的變化;(D)片吶醇產(chǎn)物的法拉第效率隨甲醇/水體積比的變化。Pinacol=紅色，縮醛=藍(lán)色，酒精=粉紅色，酸=紫色。MFB初始濃度為0.12M，電流為2.3mA，反應(yīng)時(shí)間為4h，除另有說(shuō)明外，meoh與水的體積比為5:1。圖3。采用復(fù)合相關(guān)G3(MP2)B351方法，采用DFT//M06/DZVP2等配線法計(jì)算MFB片納醇偶聯(lián)中間體的自由能面。自由基二聚(紅色)和自由基加成(藍(lán)色)途徑顯示。方案一。等離子體介導(dǎo)的片納醇偶聯(lián)的范圍總之，我們證明了等離子體-液體過(guò)程中產(chǎn)生的溶劑化電子能夠通過(guò)片吶醇偶聯(lián)反應(yīng)形成碳-碳鍵。模型底物(MFB)的參數(shù)研究表明，通過(guò)解決質(zhì)量運(yùn)輸限制，對(duì)競(jìng)爭(zhēng)酒精的選擇性是可以實(shí)現(xiàn)的。該方法的通用性延伸到其他對(duì)取代苯甲醛、芳酮和糠醛，產(chǎn)率接近40%。據(jù)我們所知，這是等離子體產(chǎn)生的溶劑化電子用于有機(jī)氧化還原耦合反應(yīng)的第一個(gè)例子，并為類似的還原有機(jī)反應(yīng)提供了一個(gè)可持續(xù)的解決方案。

經(jīng)典化學(xué)合成反應(yīng)標(biāo)準(zhǔn)操作-醇的制備1.

羧酸酯還原為醇1.1金屬鈉和醇為還原劑Thecentralneckofa5-l.three-neckedround-bottomedflaskisfittedwithastoppercarryingamercury-sealedmechanicalstirrer.Oneofthesidenecksisconnectedbymeansofashortpieceofheavyrubbertubingtoalargerefluxcondenserabout2m.long,withaninnertube2.5cm.indiameter.Thethirdneckisfittedwithaseparatoryfunnel.Intheflaskareplaced70g.(3moles)ofsodiumand200cc.ofdrytoluene.Theflaskisheatedinanoilbathuntilthesodiumismelted.Thestirreristhenstarted;whenthesodiumisfinelydivided,theoilbathisremovedandthemixtureallowedtocool.Stirringmustbecontinuedduringthecoolinginordertokeepthesodiumfinelydivided.Whenthemixturehascooledtoabout60°,thereareaddedfromtheseparatoryfunnel,first,asolutionof114g.(0.5mole)ofethyllauratein150cc.ofabsolutealcohol,then500cc.moreofalcohol,asrapidlyasispossiblewithoutlossofmaterialthroughthecondenser.Thetimerequiredfortheadditionoftheestersolutionandthealcoholislessthanfiveminutes,usuallytwoorthreeminutes.Whenthereactionhassubsided,theflaskisheatedonasteambathuntilthesodiumiscompletelydissolved.Themixtureisthensteam-distilledtoremovethetolueneandethylalcohol.Thecontentsoftheflaskaretransferredtoaseparatoryfunnelwhilestillhotandwashedthreetimeswith200-cc.portionsofhotwatertoremovethesodiumlaurate.Thelaurylalcoholisextractedwithetherfromthecooledmixtureandthewashings.Thecombinedetherextractsarewashedwithwater,sodiumcarbonatesolution,andagainwithwater,anddriedoveranhydrousmagnesiumsulfate.Theetherisevaporatedandthelaurylalcoholdistilledunderdiminishedpressure.Theyieldis60–70g.(65–75percentofthetheoreticalamount)ofaproductboilingat143–146°/18mm.or198–200°/135mm.1.2金屬氫化物為還原劑Adry,500-mL,three-necked,round-bottomedflaskisequippedwitha150-mLpressure-equalizingadditionfunnel,arefluxcondensertoppedwithaninertatmosphereline,aglassstopper,andanegg-shapedmagneticstirringbar.Theflaskischargedwithlithiumaluminumhydride(2.66g,0.070mol)andanhydrousether(50mL).Theflaskiscooledto5°Cinanice-waterbath.Asolutionofcycloadduct

2

(22.4g,0.072mol)inether(80mL)istransferredtotheadditionfunnelandaddedovera30-minperiod.Thereactionmixtureisstirredforanother15min,dilutedwithether(100mL),andquenchedbydropwiseadditionofwater(9mL).Theice-waterbathisremoved,theresultinggraysuspensionisallowedtoreachroomtemperature,andthemixtureisstirredvigorouslyforanadditional60min.Themixtureistransferredtoa1.0-LErlenmeyerflaskanddilutedwith350mLofether.Anhydroussodiumsulfate(Na2SO4)(60g)isadded,thesuspensionisstirredfor30min,andfiltered.Thefiltercakeiswashedtwicewithether(50mLeachtime).Thesolventisremovedonarotaryevaporatorandtheremainingvolatilematerialisremovedunderhighvacuumtoafford18.6g(91%)ofthedesiredaminoalcoholasaviscousclearoil.2.

羧酸還原為醇2.1LAH和硼烷還原羧酸Anoven-dried,3-L,three-neckedflaskequippedwithamechanicalstirrer,aFriedrichcondenser,andanitrogen-inlettubeisflushedwithnitrogen,andthenchargedwithasuspensionoflithiumaluminumhydride(47.9g,1.26mol)in1200mLoftetrahydrofuran(THF).Themixtureiscooled(10°C,icebath)andL-valine(100g,0.85mol)isaddedinportionsovera30-minperiodfroma200-mLround-bottomedflaskconnectedtothereactionflaskviaaflexibleplasticsleevesoasnottoproducetoovigorousanevolutionofhydrogen.Aftertheadditioniscomplete,theplasticsleeveisreplacedbyastopper,theicebathisremoved,andthereactionmixtureiswarmedtoroomtemperatureandthenrefluxedfor16hr.Thereactionmixtureisthencooledagain(10°C,icebath)anddilutedwithethylether(1000mL).Thereactionisquenchedovera30-minperiodwithwater(47mL),aqueous15%sodiumhydroxide(47mL,over20min),andwater(141mL,over30min).Thesolutionisstirredfor30minandthewhiteprecipitateisfiltered.Thefiltercakeiswashedwithethylether(3×150mL)andtheorganicfiltratesarecombined,driedwithanhydroussodiumsulfate,andconcentratedunderreducedpressure.DistillationoftheresidueundervacuumaffordsL-valinol(63.9–65.7g,73–75%)(Note5)asaclearliquid:bp63–65°C(0.9mm)(Note6):[α]D+14.6°(neat);

nD1.455;IR(neat)cm1:3300,1590;1HNMR(CDCl3)δ:0.92(d,6H),2.38–2.74(m,4H),3.13–3.78(m,2H).A2-L,three-necked,round-bottomedflaskisequippedwithamechanicalstirrer,heatingmantel,250-mLgraduatedadditionfunnel,andan8-in.,air-cooledrefluxcondenser(Westtype)toppedwithawater-cooleddistillationheadanda1-Lreceivingflask.Itisconnectedtoanitrogenlinethroughthestillhead.Theglasswareiseitheroven-driedandcooledinadesiccatororflame-driedandassembledwhilestillhot.Theassemblyisflushedwithnitrogenandchargedwith200gofL-valine(1.7mol),400mLoftetrahydrofuran(THF),and210mLoffreshlydistilledborontrifluorideetherate(242g,1.7mol).ThemixtureisheatedataratesufficienttocausetheTHFtorefluxgentlyand188mL(1.88mol)ofborane–methylsulfidecomplex(BMS)isaddeddropwiseoverthecourseof2hr.Thesolutionisthenrefluxedfor18hr.Themethylsulfidethathascollectedatthedstillheadisdiscarded,andthereactionmixtureiscooledto0°Candquenchedbytheslowadditionof200mLofmethanol.Theadditionfunnelisreplacedbyaglassstopper,andtheair-cooledcondenserisremoved,leavingtheflaskequippedfordistillationofsolventthroughthedistillationhead.Thereactionmixtureisconcentratedunderreducedpressurewithheatingandstirring.Thedistillationheadisreplacedbyawater-cooledrefluxcondenser,andtheresidueisdissolvedin1Lof6

M

sodiumhydroxideandrefluxedfor4hr.Themixtureissaturatedwithpotassiumcarbonate(ca.400g);cooled;filteredthroughaCelitepadonacoarse,frittedfunnel;andextractedwiththree1-Lportionsofchloroform.Thecombinedextractsarewashedwiththreeportionsofsaturatedsodiumchloride(5002020mLeach),stirredoveranhydrouspotassiumcarbonatefor24hr,andconcentratedunderreducedpressuretogiveayellowoil.Thecrudematerialisvacuumdistilledtogive77.5g(44%)ofpurifiedLvalinol,bp62–67°C/2.5mm;[α]D+14.6°(neat),

nD1.455;IR(neatfilm)cm?1:3300(OH),and1590(NH2);NMRδ:0.92(d,6H),1.54(m,1H),2.38–2.74(m,4H),3.13–3.78(m,2H).2.2

硼烷還原不飽和酸Adry,2-L,one-necked,round-bottomedflaskisequippedwitha1-Lpressure-equalizingfunnelandalargemagneticstirringbar.Thesystemisflame-driedunderaninternalatmosphereofdrynitrogen.Theflaskischargedwith300mLofanhydroustetrahydrofuranand100gofmonoethylfumarate.Thesolutionisthenstirredundernitrogenandbroughttoabout?5°Cusinganice–salt/methanolbath(?10°C).A1

M

solutionof700mL(0.70mol)ofborane–tetrahydrofurancomplexis

cautiously

addeddropwise(rapidH2evolutionoccurs)withrigoroustemperaturecontroltoavoidanexothermicreaction.Theice–saltbathismaintainedinpositionthroughoutthe90minofaddition.Thestirredreactionmixtureisthengraduallyallowedtowarmtoroomtemperatureoverthenext8–10hr.Thereactioniscarefullyquenchedatroomtemperaturebydropwiseadditionof1:1water:aceticacid(ca.20mL)withstirringuntilnomoregasevolutionoccurs.Thereactionisconcentratedatroomtemperatureandwaterpumppressuretoaslurrybyremovalofmostofthetetrahydrofuran.Theslurryiscarefullypouredovera20-minperiodinto300mLofice-cold,saturatedsodiumbicarbonatesolutionwithmechanicalstirringtoavoidprecipitationofsolids,andtheproductisextractedwith300mLofethylacetate.Theaqueouslayerisagainextractedwith100mLofethylacetate.Theorganiclayersarecombined,washedoncewith200mLofsaturatedsodiumbicarbonate,thendriedwellwithanhydrousmagnesiumsulfate.Solventremovalatreducedpressuregives61g(67%yield)ofessentiallypureethylhydroxycrotonate.Ananalyticalsamplemaybepreparedbyquickdistillation(orKugelrohrdistillation)at117–120°C(15mm),butthereissignificantlossofmaterialbecauseofdecompositioninthedistillationpot.From1gofproduct,0.72gofpurematerialisobtainedinthisway,andrecoverydecreasesasscaleofdistillationincreases.3.醛和酮還原成醇3.1.醛和酮還原的加氫還原Ina2-l.three-neckedflaskequippedwithastirrerandthermometerareplaced336g.(2.62moles)of3,4-dihydro-2-methoxy-4-methyl-2H-pyran(p.311),630ml.ofwater,and24ml.ofconcentratedhydrochloricacid(sp.gr.1.19).Themixtureisstirredfor2hours,duringwhichthetemperaturemayreach50°butshouldnotbepermittedtorisehigher.SolidsodiumbicarbonateisthenaddeduntilthesolutionisneutraltopHindicatorpaper(Note1).Theentirereactionmixtureweighingabout1kg.togetherwith39g.ofRaneynickel2isintroducedintoa3-l.stainless-steelrockinghydrogenationautoclave.Ahydrogenpressureofatleast1625p.s.i.(Note2)isapplied,andtheautoclaveisheatedto125°andheldtherewithshakingfor4hours.Themixtureisallowedtocoolovernight,andthecatalystisseparatedeitherbysuctionfiltrationthroughFilter-Celorbycentrifugation.Thesolutionisdistilledthrougha12-in.Vigreuxcolumn.Afterthemethanolandwaterareseparated,the3-methyl-1,5-pentanedioldistilsat139–146°/17mm.,149–150°/25mm.Theyieldis251–256g.(81–83%),

n25，1.4512–1.4521.3.2金屬還原3.2.1Na-NH3體系A(chǔ)5-L,three-necked,round-bottomedflaskisequippedwithavariablespeedHershbergstirreranda500-mLDewarcondenserfilledwithdryice–acetoneandconnectedbyitsupperjointtoamineraloilbubblerthroughwhichpassesdrynitrogengas.Theflaskisimmersedinadryice–acetonebath,flushedwellwithnitrogenand3000mLofammoniaiscondensedintotheflaskviaaglasstubepassedthrougharubberseptumintheremainingneckoftheflask.Cleansodium,125g(5.43g-atom),isaddedslowlytotheammoniawithslowstirring.Then250.3g(0.906mol)of5-methyl-2-[1-methyl-1-(phenylmethylthio)ethyl]cyclohexanoneand72.5mL(1.8mol)ofmethanolin625mLofanhydrousetherareaddeddropwiseviaapressure-equalizedadditionfunnelover5hrtothevigorouslystirred(ca.500rpm)solution.Stirringiscontinuedanadditional30minfollowingwhich150mLofmethanolisaddedover2.5hrdropwise(toavoidaviolenteruption).Thesolutionisallowedtowarmslowlyandtheadditionfunnelandthecondenserareremovedtoallowtheammoniatoevaporateovernight.Thereactionflaskisimmersedinanicebathand700mLofwaterisaddedcautiouslyoveranhourtotheyellowsolidleftbyevaporationoftheammonia.Thesolutionistransferredtoa2-Lseparatoryfunnelandextractedwithtwo200-mLportionsofether,whicharediscarded.Theaqueouslayerispouredintoamixtureof500mLofconcentratedhydrochloricacidand1000gofice,transferredtoa4-Lseparatoryfunnel,andextractedwithfour200-mLportionsofether.Thecombinedetherextractsarewashedwith200mLofwaterand200mLofsaturatedaqueoussodiumchloride,driedovermagnesiumsulfate,andconcentratedbyrotaryevaporationataspiratorvacuum.Theresidualliquidisplacedunderreducedpressure(0.2mm)for1hrtoremovetheremainingsolventtogive137–140g(80–82%)ofanorangeoilthatisadiastereomericmixtureofwhichthemajorcomponentconstitutes80%,asindicatedby13CNMR.3.2.2Na-EtOH體系Ina3-l.round-bottomedflask,fittedwithanefficientLiebigcondenser(100by1cm.),228g.(2moles)ofmethyl

n-amylketoneisdissolvedinamixtureof600cc.of95percentalcoholand200cc.ofwater.Onehundredthirtygrams(5.6gramatoms)ofsodiumintheformofwireisgraduallyaddedthroughthecondenser.Duringtheadditionofthesodiumtheflaskiscooledwithrunningwater

sothatthereactiondoesnotbecomeundulyviolent.Whenthesodiumhasdissolved,2l.ofwaterisaddedandthemixtureiscooledto15°.Theupperoilylayeristhenseparated,washedwith50cc.of1:1hydrochloricacidandthenwith50cc.ofwater,driedover20g.ofanhydroussodiumsulfate,anddistilledwithafractionatingcolumn.Afterasmallfore-runoflow-boilingliquid,thepureheptanoldistilsat155–157.5°.Theyieldis145–150g.(62–65percentofthetheoreticalamount).3.2.3Na(Hg)

體系A(chǔ)namalgampreparedfrom9.0g.(0.39atom)ofsodiumand750g.(55cc.)ofmercury(Note1)iswarmedtoabout50°(Note2)ina500-cc.Pyrexround-bottomedflask(Note3).Toitisthenaddedacoldsuspensionof25g.(0.13mole)ofxanthone(p.552)in175cc.of95percentethylalcohol.Theflaskisatoncestoppered,heldinacloth,andvigorouslyshaken,thestopperbeingraisedfromtimetotimetoreleaseanypressure.Thetemperaturerisesrapidlyto60–70°.Thesolidxanthonerapidlygoesintosolution,averyfaintandtransientbluecolorbeingdeveloped.Attheendofaboutfiveminutesthealcoholicsolutionisclearandpracticallycolorless.Afterafurtherten-minuteshakingthemercuryisseparatedandwashedwith10–15cc.ofalcohol.Thealcoholicsolutionisfilteredwhilewarmandslowlypouredwithstirringinto2l.ofcolddistilledwater.Theprecipitatedxanthydrolisfilteredwithsuction,washedwithwateruntilfreeofalkali,anddriedat40–50°toconstantweight.Thecrystallineproduct,whichweighs23–24g.(91–95percentofthetheoreticalamount),meltsat121–123°andispracticallypure(Note4)and(Note5).3.2.4Fe-HOAc體系Ina12-l.flaskfittedwithamechanicalstirrerandashortrefluxcondenserareplaced1800g.(32.2atoms)ofironfilings,3l.(52.5moles)ofglacialaceticacid,3l.ofwater,and450g.(3.95moles)ofheptaldehyde.Themixtureisheatedonthesteambath,withstirring,forsixtosevenhours.Theflaskisthenfittedtoanapparatusforsteamdistillation(p.479)andthemixturedistilledinacurrentofsteamuntilnomoreoilpassesover(7–8l.ofdistillate).Theoilisthenseparated,andtheaqueouspartdistilledtorecoverasmallquantityofdissolvedorsuspendedheptylalcohol.Thecombinedproductismixedwith1l.of20percentsodiumhydroxidesolutionandstirredonthesteambathforfourhours,inordertohydrolyzeasmallproportionofheptylacetate.Theoilisthenseparatedanddistilled,andtheportionboilingat172–176°iscollected.Theresidueintheflaskismixedwithabout100cc.ofwateranddistilled,whereuponafurthersmallquantityofoilpassesoverwiththesteam.Thisdistillateandtheforerunarefreedofthebulkofthewaterinaseparatoryfunnelanddistilledfromasmallerflask.Inthiswaythetotalyieldof

n-heptylalcoholboilingat172–176°(uncorr.)is350–370g.(75–81percentofthetheoreticalamount).Thealcoholmayberedistilledunderreducedpressure,whenitpassesoveralmostwithoutlossat71–72°/12mm.3.2.5Zn-EtOH體系Ina3-l.round-bottomedflaskfittedwithamechanicalstirrerareplaced200g.oftechnicalflakesodiumhydroxide,200g.ofbenzophenone,2l.of95percentalcohol,and200g.oftechnicalzincdust.Thestirrerisstartedandthemixtureslowlywarmstoabout70°spontaneously.Aftertwotothreehoursthemixture,whichhasstartedtocool,isfilteredwithsuction,andtheresidueiswashedtwicewith100-cc.portionsofhotalcohol.Thefiltrateispouredintofivevolumesoficewateracidifiedwithabout425cc.ofconcentratedcommercialhydrochloricacid.Thebenzohydrolseparatesasawhitecrystallinemassandisfilteredbysuction.Theyieldofcrudeair-driedproductmeltingat65°is194–196g.(96–97percentofthetheoreticalamount).From200g.ofcrudeproductin200cc.ofhotalcoholthereisobtained,aftercoolinginanice-saltmixture,filtering,anddrying,140–145g.ofproductmeltingat68°.Thebenzohydrolremaininginthemotherliquorsmaybeprecipitatedwithwater.3.3金屬氫化物還原3.3.1LAH還原Phenanthrenequinone(6g.,0.03mole)isplacedinafritted-glass(coarseporosity)extractionthimbleofaSoxhletapparatusovera1-l.flaskcontainingasuspensionof3g.oflithiumaluminumhydridein500ml.ofanhydrousdiethylether.Extractionofthequinoneoveraperiodof16hoursaffordsagreensolution.Thereactionisquenchedbythecautiousadditionofwaterandneutralizedwithglacialaceticacid.Theetherlayerisseparated,andtheaqueouslayerisextractedwithtwo200-ml.portionsofether.Thecombinedetherextractsarewashedconsecutivelywithaqueoussodiumhydrogencarbonateandwater,thendriedovermagnesiumsulfate.Evaporationofthesolventunderreducedpressuregivesthecrudeproduct,whichisrecrystallizedfrombenzene,giving3.8–4.1g.(62–68%)ofpurediol

1

asfluffy,whiteneedles,m.p.185–190°4.

手性醇的合成4.1CBS還原法A250-mL,three-necked,round-bottomedflaskisequippedwithaTeflon-coatedthermocoupleprobe,a125-mLpressure-equalizingadditionfunnel,nitrogeninlet,andTeflon-coatedmagneticstirringbar.Theflaskischargedwiththe(S)-oxazaborolidine-boranecomplex(2.91g,10.0mmol),purgedwithnitrogen,andchargedwithdrydichloromethane(10mL).Tothestirredsolutionisaddedborane-methylsulfide(10M,20mL,200mmol).Thesolutioniscooledto?20°Candtheadditionfunnelchargedwithasolutionof1-indanone(26.4g,200mmol)indrydichloromethane(75mL).The1-indanonesolutionisthenaddeddropwiseovera4–6hrperiodwhilemaintainingtheinternaltemperatureofthereactionmixtureat?20±5°C.Aftertheadditioniscomplete,thereactionmixtureisstirredfor2hrat?20°C.Afterthereactioniscomplete,themixtureiscautiouslypouredintoa1-Lflaskcontainingmagnetically-stirred,pre-cooled(?20°C)methanol(300mL).Thecoolingbathisremoved,andthestirredmixtureallowedtowarmtoroomtemperature(20–25°C).Afterevolutionofhydrogenceases,themixtureisconcentratedbydistillation(1atm)toavolumeofca.50mL.Methanol(200mL)isadded,andthedistillationrepeated.Theresiduecontainingtheproductanddiphenylprolinolisdilutedwithmethanol(100mL)andthenloadedontoa2.5×30-cmcolumnpackedwithAmberlyst15(NH+)atca.2.5mL/min,collecting40-mLfractions.Thecolumnisrinsedwithmethanoluntiltheproductiseluted.Thecolumnisthenrinsedwith1Mmethanolicammoniauntilthediphenylprolinoliseluted.Thefractionscontainingtheproduct(2–15)arecombined,andthenconcentratedunderreducedpressure(40°C,100mm)togive26.2gofcrudeproductasawhitecrystallinesol